Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) - Volume 11, Issue 2, 2011

Stroke, either ischemic or hemorrhagic, is the leading cause of adult disability and the second leading cause of death worldwide. According to The World Stroke Organization, one in six people alive today will at some time have a stroke, and every six seconds someone somewhere will die from a stroke. Therefore, the fight against stroke has been put at the top of the global health agenda, and having up-to-date information is cruc Read More

Stroke is the third leading cause of mortality and disability in the United States. Ischemic stroke constitutes 85% of all stroke cases. However, no effective treatment has been found to prevent damage to the brain in such cases except tissue plasminogen activator with narrow therapeutic window, and there is an unmet need to develop therapeutics for neuroprotection from ischemic stroke. Studies have shown that mecha Read More

Due to a lack of efficient treatments, searching for novel therapies against acute ischemic stroke represents one of the main fields in neuropharmacology. In this review we summarize and discuss the role of mitochondrial participation in ischemia-induced neuronal death. Mitochondria are regarded as the main link between cellular stress signals and the execution of programmed death of nerve cells. Since Read More

Cerebral ischemia is characterized by obvious inflammatory cell aggregations, up-regulation of cytokine expression, and increased expression of intercellular adhesion molecules. Like systemic bacterial infections, cerebral injury is also associated with innate immunity, a specific immunologic response that utilizes Toll-like receptors (TLRs). The involvement of TLRs in cerebral ischemia is now being confirmed using animal mode Read More

Selective neuronal cell death is one of the major causes of neuronal damage following stroke, and cerebral cells naturally mobilize diverse survival signaling pathways to protect against ischemia. Importantly, therapeutic strategies designed to improve endogenous anti-apoptotic signaling appear to hold great promise in stroke treatment. While a variety of complex mechanisms have been implicated in the pathogenesis of Read More

Histone deacetylases (HDACs) play a key role in the homeostasis of histone acetylation and gene transcription. Histone hypoacetylation and transcriptional dysfunction have been identified in a large number of neurological diseases, including ischemic and hemorrhagic stroke. HDAC inhibitors (HDACi) have emerged as a promising therapeutic intervention in neurodegenerative disorders. Here we review and discuss re Read More

Intracerebral hemorrhage (ICH) is associated with a high mortality and severe disability. Whereas a classical open craniotomy for hematoma removal may further traumatize brain tissue, minimally invasive surgery combines benefits of surgical clot removal with limited tissue damage and shorter surgery duration. Evacuation is often hampered by clot retraction, thus, advocating clot liquefaction to facilitate complete evacu Read More

Human adult skeletal stem cells, a.k.a. mesenchymal stem cells or marrow stromal cells (MSCs), have been identified as precursors of several different mesenchymal cellular lineages, including osteoblasts, chondrocytes, myoblasts, adipocytes, and fibroblasts, as well as non-mesenchymal lineages including neurons and glial cells. Adult stem cell transplantation is a promising strategy for the treatment of stroke. MSCs are al Read More

In the past two decades, over 1000 clinical trials have failed to demonstrate a benefit in treating stroke, with the exception of thrombolytics. Although many targets have been pursued, including antioxidants, calcium channel blockers, glutamate receptor blockers, and neurotrophic factors, often the focus has been on neuronal mechanisms of injury. Broader attention to loss and dysfunction of non-neuronal cell types Read More